Pyrazole

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A novel bridged binuclear Cu(II) complex with mixed ligands, di-μ-(2-aminopyridine(N,N′))-bis[(2,6-pyridinedicarboxylate)aquacopper(II)] tetrahydrate, formulated as [Cu(μ-ap)(dipic)(H2O)]2·4H2O (1) (dipic = 2,6-pyridinedicarboxylate, ap = 2-aminopyridine), has been synthesized and characterized by elemental, spectral (IR and UV–Vis.), thermal analysis, magnetic measurements and single crystal X-ray diffraction analysis. The central Cu(II) ion resides on a centre of symmetry in a distorted square-pyramid coordination environment comprising of two N atoms, one from dipic and one from the ap ring, two carboxylate O atoms from dipic, and one O atom from water. Intermolecular N–H⋯O and O–H⋯O hydrogen bonds and π–π stacking interactions seem to be effective in the stabilization of the crystal structure. The free ligands and the complex were also evaluated for their antimicrobial and radical scavenging activities (DPPH = 1,1-diphenyl-2-picrylhydrazyl hydrate) using in vitro microdilution methods. Antimicrobial screening of the free ligands and their complex showed that the free ligands and the complex possess antifungal activity against Candida sp.

The reactions of 2-aminothiophenol with acetylacetone in refluxing DMSO or ethanol was investigated. Treatment of 1 with enaminone 5 gave benzothiazine derivative 6. A reasonable mechanism to account for the formation of pyridone derivative 11 by treatment of 2 with malononitrile. Reactions of 2 with cyanoacetic hydrazide, thiosemicarbazide, and hydrazine hydrate and phenyl hydrazine afforded the compounds 13, 15 and, 17a-b respectively. Condensation of 13 with 4-methoxy benzaldehyde gave 18. The latter compound reacted with malononitrile gave pyridone derivative 19. A reasonable mechanism account for the formation of pyrazolo[3,4-b]pyridine derivative 20 from the reaction of 13 with DMF-DMA via cleavage of a thiazine ring of benzothiazine. The structures of all newly synthesized compounds elucidated by elemental analysis 1 H-NMR and 13 C-NMR spectra, Ms and X-ray crystallographic investigations. The reported crystal structures of these novel benzothiazine derivatives are expected to be a remarkable contribution to the crystallographic database of heterocyclic compounds.

A series of fourteen novel 1,3,4-triarylpyrazoles were synthesized and evaluated for their antiproliferative activity against human breast cancer MCF7 cell line. Cells were exposed to different concentrations of compounds (0.1, 10, 100, 1000 µM) for 72 hours. Then the viability of treated cells was determined using MTT technique. Compound 7a was found to exhibit significant antiproliferative activity (IC50 = 6.95 μM). Using flow cytometric analysis, compound 7a was observed to induce apoptosis and to block the cell cycle at G2/M phases in MCF7 cells. 3D-Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explore the structural requirements controlling the observed anti-tumor properties.

A series of new 1-(1H-benzo[d] imidazol-2-yl)-3-methyl-4-(substituted phenylhydrazono)-1H-pyrazol-5(4H)-ones (4a-i)  were synthesized by the condensation of 2-hydrazinyl-1H-benzo[d]imidazole (2) with ethyl-2-arylhydrazono-3-oxobutyrates (3a-i)  in glacial acetic acid. Also,        3-(1H-benzo[d]imidazol-2-ylamino)-2-(7-hydroxy-substituted-2-oxo-2H-chromen/quinolin -3-yl)thiazolidin-4-one)s (7a-d) were prepared via the cyclisation of Schiff bases 3-((2-(1H-benzo[d]imidazol-2-yl)hydrazono)substituted)-7-hydroxy-4-methyl-2H-chromen/quinolin-2-one          (6a-d) with thioglycolic acid in refluxing benzene. Structural assignments of these synthesized compounds were based on IR, 1HNMR, and Mass spectral data. The newly synthesized compounds (4a-i), (6a-d) and (7a-d) which possess a variety of heterocycles with benzimidazole as core nucleus were evaluated for their antimicrobial and anti-inflammatory activities by cup-plate method and formalin induced rat hind    paw oedema method respectively.

The action of synthetic low molecular weight compounds — pyrazole derivatives — on the growth and deve-lopment of tomato plants (Solanum lycopersicum L.) of the Money Maker cultivar in vivo and in vitro is stu-died. It is found that the compound D-pyrazole-3 at a concentration of 10–8 М demonstrates the most pronounced action on the growth and development of tomato plants in vivo. The effect of these compounds on the morphogenetic potential of S. lycopersicum explants in vitro is studied for the first time, and it is found that compounds D-pyrazole-1, D-pyrazole-2 and D-pyrazole-3 effectively induce callusogenesis and rhizogenesis, as well as, depending on the concentration, direct plant regeneration in vitro. Under the action of all three compounds, both at a concentration of 10–9 М and 10–8 М, the most effective root formation occurs on shoot explants. For the direct plant regeneration from this type of explants, the most effective compounds are D-pyrazole-1 at a concentration of 10–9 М or D-pyrazole-2 at a concentration of 10–8 М, which can then be re-commended for the use in the biotechnological research of the genetic improvement of S. lycopersicum.
Кeywords: plants, Solanum lycopersicum L., plant growth regulators, pyrazole derivatives,  auxin, in vivo, in vitro.

New  series  of  2-heterocycle-substituted  benzimidazole  having  a
pyrazolo  [3,  4-d]  pyrimidine  nucleus  have  been  synthesized  by
reacting  2-(chloromethyl)  benzimidazole  with  hydrazine  hydrate  to
form  compound  (1).  The  vital  compound  in  this  synthesis  1-((benzoimidazol-2-yl)methyl)-3-methyl-pyrazol-5-one was  obtained
by  reacting  compound  (1)  with  ethyl  acetoacetate,  and  was  used  in
the Biginelli multi-component cyclo condensation reaction with eight
derivatives of benzaldehyde in presence of urea  to  form pyrimidine
derivatives (3-10).
The products were characterized by C.H.N analyses,  I.R spectra and
1
HNMR spectrum.
Antibacterial activity of some prepared compounds against two types
of  bacteria: Staphylococcus  aureus (Gram  positive)  and
Pseudomonas  aeruginosa (Gram  negative).  Some  the  compounds
showed high inhibition activity against bacteria.

Four-component reactions of 3-amino-1,2,4-triazole or 5-amino-1H-pyrazole-4-carbonitrile with aromatic aldehydes and pyruvic acid or its esters under ultrasonication were studied. Unusual for such a reaction type, a cascade of elementary stages led to the formation of 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines.

The comparative analysis of the stimulating effect of low molecular weight heterocyclic compounds, derivatives of pyrimidine, pyrazole, isoflavones, pyridine, oxazolopyrimidine, oxazole and plant hormones auxins IAA (1H-Indol-3-ylacetic acid) and NAA (1-Naphthylacetic acid) on germination of seeds and growth of seedlings of flax (Linum usitatissimum L.) cultivars Ukrainian 3 and Svitanok was conducted. The specific auxin-like stimulating effect of chemical heterocyclic compounds on the basic processes of flax seedlings growth: cell division, cell proliferation, cell elongation and cell differentiation was found. The growth parameters of flax seedlings grown on water solution of chemical heterocyclic compounds used at the concentrations 10-8 M and 10-9 M were similar or higher of the growth parameters of flax seedlings grown on distilled water (control) or on water solution of auxins IAA and NAA used at the same concentrations 10-8 M and 10-9 M. The obtained results proved the possibility of practical application o f derivatives of pyrimidine, pyrazole, isoflavones, pyridine, oxazolopyrimidine and oxazole for intensification of vegetative growth of flax.
Keywords: Linum usitatissimum L., auxins IAA and NAA, pyrimidine, pyrazole, isoflavones, pyridine, oxazolopyrimidine, oxazole.

In the present study, a series of novel pyrazole‐thiazole hybrids (4a‐l) were designed, synthesized and assessed for their in vitro antimicrobial activity against both Gram‐positive and Gram‐negative pathogenic bacterial and fungal strains. Compounds derived from p‐CH3 phenyl (4b), p‐Br phenyl (4g), 8‐bromocoumarinyl (4k), and 6,8‐dibromocoumarinyl (4l) exhibited promising inhibitory activity against the tested bacterial strains with minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) spectrum of 1.9/7.8 μg/mL to 3.9/7.8 μg/mL. The compounds with p‐CH3 phenyl (4b), p‐OCH3 phenyl (4c), benzo[f]coumarinyl (4j), 8‐bromocoumarinyl (4k) substitutions showed their inhibitory potency against various Candida strains with MIC/minimum fungicidal concentration (MFC) values of 3.9/7.8 μg/mL. Also, anti‐biofilm and toxicity profile of the compounds was also tested. The biofilm inhibition results revealed that the compound 4 j exhibited promising activity with an IC50 value of 11.8 μM against S. aureus MTCC 96, while 4 k showed significant activity against S. aureus MLS16 MTCC 2940, K. planticola MTCC 530 and C. albicans MTCC 3017 with IC50 values of 12, 14 and 16 μM, respectively. The present study has emphasized that thiazole‐pyrazole hybrids with benzothiazole and coumarin scaffolds can be a novel and potent class of molecules with potential biological activities.

Synthesis and biological assessment of six novel 2-substituted mercaptobenzimidazole derivatives is performed. The title compounds are characterized by their analytical and spectral data. All the synthesized compounds are screened for their anti-ulcer and anti-microbial activity. 2-(1H-benzimidazole-2-sulfinyl) –N-(4-benzyloxy-phenyl)-acetamide, N-(4-benzyloxy-phenyl)-4-(1H-benzimidazole-2-sulfinyl)-butyramide, N-(4-benzyloxy phenyl)-4-(5-methoxy 1H-benzimidazole-2-sulfinyl)-butyramide showed significant antiulcer activity. All the compounds moderate antibacterial and antifungal activity.

The evaluation of the cytotoxic properties in vitro of three synthetic tripods containing pyrazole: N,N-bis[(3,5-dimethylpyrazol-1-yl)methyl]aniline (1); N,N-tetrakis[(3,5-dimethylpyrazol-1-yl)methyl]-para-phenylenediamine (2); and N,N-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl]-para-phenylenediamine (3), was examined for their cytotoxic activity on two tumor cell lines: P815 (murin mastocytoma) and Hep (human laryngeal carcinome). While the compound 2 shows a small cytotoxic activity, compounds 1 and 3 are more cytotoxic against both cell lines. However, this cytotoxicity is more pronounced against Hep cell line (IC50: 3.25 microg mL(-1) for compound 1 and 6.92 microg mL(-1) for compound 3) than P815 cell line (IC50: 17.82 microg mL(-1) for compound 1 and 37.21 microg mL(-1) for compound 3). Statistical analysis shows that the compound 1 is two- to threefold more cytotoxic than compound 3 (P < 0.05). Interestingly, the cytotoxicity induced by compound 1 against Hep cell line is more important than that induced by adriamycin used as a positive control.

Background: Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Methods: Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. Results: All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI 50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI 50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI 50 value of 0.34 µM. Conclusion: The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at benzofuran of reference compound N-acetyl pyrazoline derivative might be valid for contributing to anti-cancer activity.

Abstract A series of pyrazole based aurone analogs 3(a-n) have been synthesized and evaluated for their cytotoxic activity against MCF-7 cell line. All the products have been obtained by solid phase reaction and organic solvent free simple work-up procedure. Structures of the synthesized aurones were confirmed by their IR, 1H-NMR, 13C-NMR, elemental analysis and mass spectrometry data. The cytotoxic activity of these compounds was assessed by MTT assay and the nine products were found to be potential inhibitors against human breast adenocarcinoma cell line i.e. MCF-7. Aurone analogs 3a, 3b, 3c, 3e, 3i and 3n are the most active against the MCF-7 cell line with IC50 of 13.8, 15.8, 4.3, 2.7, 12.9 and 15.5μg/mL respectively, as compared to paclitaxel, with an IC50 value of 18.5μg/mL. Cytotoxicity against MCF-7 cancer cells, makes these molecules attractive candidates for the potential anticancer drug.

... have been missed. The homoleptic dithiophosphates, Ni[S 2 P(OR) 2 ] 2 , (R = Me [2], Et [3], n-Pr [4], iso-Pr [5], iso-Bu [6], cyclo-C 6 H 11 [7], benzyl, ortho-tolyl, meta-tolyl [8], para-tolyl [9]) are square-planar complexes. Many six ...

A highly efficient and environmentally benign protocol has been developed for the construction of dihydropyrano[2,3-c] pyrazole derivatives through one-pot, multi-component cascade reaction of various aldehydes, acetoacetic ester, hydrazine hydrate and malononitrile under microwave irradiation using L-Tyrosine as catalyst in the presence of green solvent medium (ethanol-water) is described. The significant feature of this protocol is the use of ethanol-water as a green solvent system.

Ligand size and valency strongly influence the receptor uptake and clearance of tumor angiogenesis imaging agents. The structures of successful imaging agents exhibit a high degree of variability, encompassing small mono-valent arginine-glycine-aspartic acid (RGD)-containing peptides, multivalent RGD-oligomers, and a monoclonal antibody against integrin alpha-v-beta-3 (αvβ3). We have pursued a nano-scale approach to imaging of angiogenesis using rationally designed polyamidoamine (PAMAM) dendrimers covalently adorned with RGD-cyclopeptides. An orthogonal oxime-ligation strategy was applied to chemoselectively effect conjugation of the PAMAM dendrimers with RGD-cyclopeptides for targeting αvβ3. Fluorescent dyes for optical imaging and chelates for gadolinium-based magnetic resonance (MR) imaging were subsequently appended to create robust multimodal macromolecular imaging agents. Fluorescence microscopy revealed selective binding of the resulting RGD peptide-bearing dendrimer with empty chelates to αvβ3-expressing cells, but somewhat reduced selectivity was observed following Gd(III) complexation. The expected incomplete saturation of chelates with Gd(III) ions permitted radiometal complexation, and an in vivo tissue distribution of the resulting agent in M21 melanoma tumor-bearing mice showed mostly renal and reticuloendothelial accumulation, with the tumor:blood ratio peaking (3.30 ± .03) at 2 hr post-injection.

A one-pot, three-component, microwave-assisted reaction of polysubstituted 5-aminopyrazoles, triethyl orthoformate, and a series of cyclic secondary amines was developed and successfully employed for the synthesis of novel N-pyrazolylformamidines. Under catalyst-free conditions, the reaction proceeded in a chemo- and regioselective manner, resulting in the formation of unsymmetric formamidines, which were isolated in high yields and purity. Some of the prepared compounds were found to inhibit interleukin-17 secretion in phenotypic in vitro assays.

A new series of triheterocyclic compounds containing pyrazole, pyran, and pyrimidinone rings was
synthesized via a one-pot condensation of ethylacetoacetate, hydrazine hydrate, barbituric acid, and
aromatic aldehydes in the presence of catalytic amounts of titanium dioxide nanowires. Various
functional groups were well tolerated under the optimized reaction conditions.